The phagocyte NADPH oxidase complex plays a crucial role in host defense against microbial infection through the production of superoxides. Chronic granulomatous disease (CGD) is an inherited immune deficiency caused by the absence of certain components of the NADPH oxidase. Key to the activation of the NADPH oxidase is the cytoplasmic subunit p47phox, which includes the tandem SH3 domains (N-SH3 and C-SH3). In active phagocytes, p47phox forms a stable complex with the cytoplasmic region of membrane subunit p22phox that forms a left-handed polyproline type-II (PPII) helix conformation. In this report, we have analyzed the conformational changes of p47phox-p22phox complexes of wild-type and three mutants, which have been detected in CGD patients, using molecular dynamics simulations. We have found that in the wild-type, two basal planes of PPII prism in cytoplasmic region of p22phox interacted with N-SH3 and C-SH3. In contrast, in the modeled mutants, the residue at the ape of PPII helix, which interacts simultaneously with both of the tandem SH3 domains in the wild-type, moved toward C-SH3. Furthermore, interaction energies of the cytoplasmic region of p22phox with C-SH3 tend to decrease in these mutants. All these findings led us to conclude that interactions between N-SH3 of p47phox and PPII helix, which is formed by cytoplasmic region of p22phox, may play a significant role in the activation of the NADPH oxidase. 相似文献
The relationships between the viscoelastic and structural properties of glass-forming materials with polysiloxane bonds, which serve as network formers, and phenyl groups, which act as network terminators, are examined based on shear viscoelasticity, (29)Si MAS NMR, and GPC measurements during the early stages of the network-forming process. The viscosities of the present samples do not depend on the frequency at temperatures up to 200 degrees C, suggesting that the origin of the viscous flow does not include intermolecular entanglement. According to the results of the strain dependence of the elastic modulus, the bridging-oxygen number, and molecular weight, the present polysiloxane system has a complex structure, or distribution of various-sized molecules composed of a polysiloxane network with various dimensionalities, and furthermore an elementary process of the viscosity is simple flow of these molecules. The structural factors that determine the viscosity and its temperature dependence are categorized into the molecular size and the intramolecular structure by using a theory based on the free-volume model. The relationship between the viscosity and the structure around the glass transition temperature is quantitatively examined and it is concluded that introducing larger numbers of Ph groups makes the viscosity less sensitive to structural factors. 相似文献
[reaction: see text] The reaction of a variety of indoles with N-thioalkyl- and N-thioarylphthalimides to produce 3-thioindoles is reported. Catalytic quantities of halide-containing salts are crucial to the success of this reaction. This highly efficient reaction provides sulfenylated indoles from bench-stable, readily available starting materials in good to excellent yields. 相似文献
A simple method for the determination of magnesium stearate in capsule- or tablet-type supplements was developed. Free stearic acid in the sample was removed by extraction with tetrahydrofuran. The remaining stearate was converted to stearic acid by reaction with a cation-exchange resin. The resulting stearic acid was determined by gas chromatography with a polar column. Esters of stearic acid were not converted to stearic acid and would not cause a positive error in the amount of stearate. The amount of magnesium stearate was calculated based on the stearic acid concentration thus obtained. Magnesium stearate levels in 5 out of 25 supplements exceeded 2500 microg/g, which indicated the possible admixture of magnesium stearate. 相似文献
Lymphocytes in T cell activation require extracellular nutrients to provide energy for cellular proliferation and effector functions. Therefore, inhibitors of nutrient transporters are expected to be a new class of immunosuppressant. Here, we report that the molecular target of brasilicardin A (BraA), an immunosuppressive compound, is the amino acid transporter system L. BraA inhibited the cell-cycle progression of murine T cell lymphocyte CTLL-2 cells in G1 phase, and potently inhibited the uptake of amino acids that are substrates for amino acid transport system L. Moreover, BraA stimulated the GCN2 activation and, subsequently, the phosphorylation of eIF2alpha. These results suggest that the immunosuppressive activity of BraA is induced by amino acid deprivation via the inhibition of system L and that the amino acid transporter is a target for immunosuppressant. 相似文献
The reaction coordinate of the S(1)-S(0) internal conversion of azulene has been analyzed using ab initio complete active space self-consistent field method. The stable geometry in S(0) (S(0) geometry) takes a bond-equalized structure where all the peripheral skeletal bond distances are similar to an aromatic CC bond distance. The transannular bond is similar to a normal C-C single bond. The first event upon electronic excitation into S(1) at S(0) geometry is characterized by the following two simultaneous changes in the skeletal bonds; the transannular bond in S(1) increases its double bond character and the aromaticity of the peripheral bonds disappears. In consequence, the most stable azulene in S(1) (S(1) geometry) has a biradical character. To reach the conical intersection between S(1) and S(0) (S(1)S(0)-CIX) where radiationless relaxation takes place, the seven-membered ring greatly deviates from a planar structure. After a transition into S(0) at S(1)S(0)-CIX, the bond-equalized structure is recovered immediately and then the nonplanarity decreases so that azulene again takes the stable planar S(0) geometry. In order to deepen the understanding of the S(1)-S(0) internal conversion, the dipole moments along the reaction coordinate have been analyzed. 相似文献
In this study, the feasibility of introducing redox property to an amphiphilic phospholipid polymer (PMBN) was investigated.
The active ester group in the side chain of the polymer was used to react with pyrroloquinoline quinine (PQQ). Redox peaks
that corresponded to PQQ redox potentials were observed after the modification. Glucose oxidase was immobilized to the modified
polymer. Electrochemical oxidation of glucose was carried out with the polymer electrode. The oxidation current increased
with elevating glucose concentration indicating electron transfer established between the electrode and enzyme. It suggests
that by modification, PMBN is possible to use for enzyme electrode for bioelectronics. 相似文献
We have discovered that an Ir‐23Nb binary alloy more effectively oxidizes hydrogen peroxide than Ir, Ir‐13Nb, Ir‐17Nb, Ir‐30Nb, Ir‐43Nb, Ir‐62Nb, or Nb. The oxidation capability was determined via cyclic voltammogram measurements of pH‐buffer and hydrogen peroxide. We ascertained that applying a 0.7 V potential produces hydrogen peroxide currents of 9.2 μA/mm2 Ir‐23Nb, 5.3 μA/mm2 Ir, 5.1 μA/mm2 Ir‐17Nb, 3.7 μA/mm2 Ir‐13Nb, 2.0 μA/mm2 Ir‐30Nb, 1.5 μA/mm2 Ir‐43Nb, 0.6 μA/mm2 Ir‐62Nb, and 0.13 μA/mm2 Nb. These results indicate that the effective oxidation of Ir‐23Nb for hydrogen peroxide might be due to its fcc+L12 two‐phase structure and that Ir‐23Nb can be used as an amperometric transducer material. 相似文献
DNA duplexes containing 5‐modified uracil pairs (5‐bromo, 5‐fluoro, and 5‐cyanouracil) bind selectivity to metal ions. Their selectivity is sensitive to the pH value of the solution (see picture), as the acidities of the modified uracil bases vary according to the electron‐withdrawing properties of the substituents.
A simple interferometric polarimeter with an integrated calibration scheme is proposed for accurate and fast mapping of the state of polarization (SOP). Conventional single-shot polarimeters that detect the amplitude and phase of orthogonally polarized field components by interferometry using Fourier fringe analysis suffers from errors caused by the imperfect reference beam and ambiguity in the spatial carrier frequency in the fringe pattern. In the proposed system, the integrated calibration scheme eliminates those error sources and enables accurate measurement of SOP without prior knowledge of the reference beam and the spatial carrier frequency. 相似文献